I really don't have time for posters who lack common decency and respect... the ignore function is well and truly being utilised by me to save me from wasting any time reading posts from little keyboard warrior brats. Appreciate the supportive posts by the HC community, but I've got some tough skin ... water off a swan's back!
Seems like there are some detectives among us searching for clues... sounds like a bit of fun, here's my contribution.
Apart from the phase 2 trial... I believe the biggest clue was given by the results of the LVAD trial, where Revascor was used on end-stage ischemic and non-ischemic heart failure patients who had an LVAD.
Whilst the primary endpoint of that NIH funded trial was not met, the data generated from that trial was invaluable. I say this because the NIH funded trial was a 2:1 randomised controlled trial with 159 patients (phase 2b)... and it showed a 76% reduction in gastrointestinal bleeding (GI) bleeding at 6 months (P<0.001), and a 65% reduction in associated hospitalisations, and ischemic patients benefitted more than non-ischemic patients.
The market didn't quite understand what that meant at the time, but the FDA have since confirmed that reduction in GI bleeding on LVAD patients was an approvable primary endpoint, and whilst it wasn't sufficient for accelerated approval (they tried under RMAT designation), the FDA said it was approvable following a confirmatory trial (which hasn't happened yet given the pandemic).
So what is the significance of all this... well let me firstly take a step back and put forth a key doubt cast on Mesoblast's MPCs therapy by critics... that is, MPCs don't actually do anything... you inject them into your body/organ, and the MPCs get flushed out of your body.
To date, the 159 patient randomised controlled trial run by the NIH is the largest clinical trial read-out for Revascor... and guess what, it did something... it did something very significant, something the FDA is willing to approve the use of Revascor for GI bleeds on LVAD patients (if confirmatory trial results confirm the outcomes of the first trial).
So here we have objective gold-standard clinical data suggesting that injecting Revascor into a human body does in fact result in a clinical benefit. This is a lot more informative than say the futility analysis which took place in 2017 as the bar for that analysis would have been relatively low to continue the trial... clinical data from another trial carries much more weight IMO.
But how does this translate to our current phase 3 trial that is about to read-out?
Where the phase 2b LVAD trial enrolled both non-ischemic and ischemic patients... the Phase 3 trial patients are mostly ischemic patients, which responded best to Revascor in the phase 2b trial... from what I recall, if the phase 2b trial only enrolled ischemic patients in their trial.. they would have met their primary end-point for weening off the LVAD (p<0.02), but whilst that means little in the phase 2b trial... how that translates to how the mostly ischemic patients in the phase 3 advanced CHF trial will respond to Revascor... well it appears to suggest that Revascor does have some beneficial impact on these patients.
We've discussed the phase 2 clinical data in some detail... and if those were to be looked at in isolation, then there are definitely reasons to doubt a large scale phase 3 trial would show meaningful clinical benefit. But I believe if you take into account the LVAD trial results... it substantially increases the likelihood of a positive read-out for our phase 3 trial.
This coupled with other little clues...
1. results not being published at the AHA in November (where bad results were likely to have been read-out);
2. how long it took for the trial to reach it's required events (suggesting a large portion of the patients enrolled in the trial were performing better than expected);
3. an enriched class III patient population (where clinical benefit would be most obvious i.e. control patients have a very high likelihood of events, providing a very obvious contrast to patients who have experienced clinical benefit through Revascor);
4. an adaptive event-driven trial design that will give this trial the best chance of detecting any clinical benefit from the use of Revascor with advanced CHF; and
5. the lead investigator's comments around seeing something happening with the patients enrolled in this trial through his own experience in the clinical trial.
To balance things out... the potential red flags (and my thoughts on them) to be aware of are IMO:
1. stem cells in general are largely unproven in large scale phase 3 randomised controlled trials.. in fact this phase 3 CHF trial is the largest ever run... in simple terms, it's risky as there are so many unknowns;
2. the results are taking a long time to be released, and whilst this is normally a bad sign .. there are very rational reasons why this may be the case i.e. pandemic has meant the data was not ready for analysis until much later in the year (May vs Aug is my estimate) and that management simply did not have the bandwidth to deal with COVID-ARDS, Ryoncil FDA approval / ODAC process and two phase 3 read-outs at the same time... it is totally within reason that management made a conscious decision to prioritise COVID-ARDS (we knew about the trial and manufacturing scale-up issues, but what we didn't know was the negotiations happening in the background with Novartis ... they kept that extremely well guarded) as well as Ryoncil first... and once they had the capacity, they would dedicate their time to CLBP and CHF .. as rushing their analysis and/or data release would not do these two very critical & potential blockbuster programs justice.
3. Very little content on CHF and CLBP ever since COVID-ARDS came about (there really isn't much to talk about before results are released for CLBP and CHF... they've spent years reinterring the same content... the market is clearly focused on Ryoncil and COVID-ARDS as there is actually progress (good or bad) being made with these programs, so the slide decks and analyst calls are logically focused on these.
Goodluck all
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